Amit Singh

Summary

Affiliation: University of Dayton
Location: Dayton, USA
URL: http://udbiology.com/content.php?id=691
Summary:
Drosophila eye model to study axial patterning, cell survival & birth defects.

The fruit fly, Drosophila melanogaster, eye serves as an excellent model to study cell type specification during development. Drosophila eye has been extensively used to address diverse biological processes like patterning cell proliferation, cell death, cell survival, polarity and genetic basis of human diseases. The compound eye of an adult fly develops from the primordium called eye imaginal disc harbored inside larva, which initiates from a group of 20- cells as early as an embryo (Fig. 1).



Fig.1 The compound eye of Drosophila comprising of 800 unit eyes, ommatidia, initiates from eye-antennal (E.A.) primordium present in the embryo (A), which grows into larval E.A imaginal disc (B). E.A imaginal disc give rise to adult eye (C), which comprises of dorsal (red) and ventral (blue) compartments antenna (green) and adult head structures. (Dorsal up and ventral down).
























Axial Patterning: Dorso-ventral patterning in Drosophila eye.
























Axial patterning is hallmark of organogenesis which results in transition of a single sheet of cells into a 3-D organ. Our lab is interested in understanding the molecular genetic basis of the Dorso-ventral patterning, the first lineage restriction event of early eye primordium. DV patterning thus plays a crucial role in inducing growth and patterning of early eye disc. The dorsal and ventral domains of the eye are generated by the domain specific expression and function of the dorsal selector genes and the ventral growth controlling genes. Our results show that antagonistic interactions between dorsal and ventral genes define the dorso-ventral eye boundary or equator. Our lab will focus on identifying new components of DV patterning and their role in retinal determination of the eye.



Fig. 2. Ventral is the ground state of the early eye. Early larval eye primordium arises from an initial ventral state which require ventral gene function. Later, when dorsal genes expression emerges in the eye disc Dorsal-Ventral (DV) axis specification of the eye takes place. DV axis is the first axis defined in Drosophila eye (Singh & Choi, 2003)

Cell Survival:
Early development of an organ primordium is marked by the rapid growth phase until a threshold of cell number is attained which allow differentiation process to begin. Our interest is to identify the genes which are required for cell survival during this early rapid growth phase. We have found that DV patterning genes also play this crucial role of cell survival during early eye development. Our focus would be to understand the mechanism and to identify the downstream components of this pathway.

Birth defects:
"Birth defects are the single leading cause of infant mortality. While weve made great strides in recent years, the causes of over 70 percent of birth defects remain unknown. The collective habilitation costs for these children surpass $1 billion dollars annually, a cost that pales to insignificance when compared to the physical and psychological impact of these birth defects on the affected children and their families. Despite unprecedented strides in molecular genetics, brought about through sequencing of the human genome, the causes of greater than 60% of all birth defects remain unknown. Our laboratory seek to provide a better understanding of the molecular, genetic, and environmental basis of normal eye development, as well as elucidate the genes and molecules that when altered result in the genesis of birth defects in eye.





Grants:
1R15HD064557-01
Genetic Control of Axial Patterning in Drosophila Eye

Ohio Cancer Seed grant
Publications:
1. Oros SM, Tare M, Kango-Singh M, Singh A.2010.Dorsal eye selector pannier (pnr) suppresses the eye fate to define dorsal margin of the Drosophila eye. Dev Biol. 2010 Oct 15;346(2):258-71. Epub 2010 Aug 5.PMID:

2.Kango-Singh M, Singh A.2009. Regulation of organ size: insights from the Drosophila Hippo signaling pathway.
Dev Dyn. 2009 Jul;238(7):1627-37. Review.
PMID:

3.Lim J, Lee OK, Hsu YC, Singh A, Choi KW. (2007). Drosophila TRAP230/240 are essential coactivators for Atonal in retinal neurogenesis. Dev Biol. 2007 Aug 15;308(2):322-30. Epub 2007 May 26. PMID:

4. Singh A, Shi X, Choi KW. (2006).Lobe and Serrate are required for cell survival during early eye development in Drosophila. Development. 2006 Dec;133(23):4771-81. PMID:

5.Singh A, Chan J, Chern JJ, Choi KW.(2005). Genetic interaction of Lobe with its modifiers in dorsoventral patterning and growth of the Drosophila eye.Genetics. 2005 Sep;171(1):169-83. Epub 2005 Jun 23. PMID:

6. Singh A, Kango-Singh M, Choi KW, Sun YH. (2004).Dorso-ventral asymmetric functions of teashirt in Drosophila eye development depend on spatial cues provided by early DV patterning genes. Mech Dev. 2004 Apr;121(4):365-70. PMID:

7. Kango-Singh M, Singh A, Henry Sun Y.(2003). Eyeless collaborates with Hedgehog and Decapentaplegic signaling in Drosophila eye induction. Dev Biol. 2003 Apr 1;256(1):49-60.
PMID:

8. Singh A, Kango-Singh M, Sun YH.(2002).Eye suppression, a novel function of teashirt, requires Wingless signaling.
Development. 2002 Sep;129(18):4271-80. PMID:.The wings of Bombyx mori develop from larval discs exhibiting an early differentiated state: a preliminary report.

9. Kango-Singh M, Singh A, Gopinathan KP.(2001). The wings of Bombyx mori develop from larval discs exhibiting an early differentiated state: a preliminary report.J Biosci. 2001 Jun;26(2):167-77. PMID:

10. Singh A, Kango M, Sinha P. (1995). An improved method for chemical devitellinization of X-gal stained Drosophila embryos. Indian J Exp Biol. 1995 Feb;33(2):150-2. PMID:7538973

Publications

  1. ncbi request reprint An improved method for chemical devitellinization of X-gal stained Drosophila embryos
    A Singh
    Drosophila Stock Center, School of Life Science, Indore, India
    Indian J Exp Biol 33:150-2. 1995
  2. pmc Dorsal eye selector pannier (pnr) suppresses the eye fate to define dorsal margin of the Drosophila eye
    Sarah M Oros
    University of Dayton, Dayton, OH 45469, USA
    Dev Biol 346:258-71. 2010
  3. doi request reprint Regulation of organ size: insights from the Drosophila Hippo signaling pathway
    Madhuri Kango-Singh
    Division of Basic Sciences, Mercer University School of Medicine, Macon, Georgia 31207, USA
    Dev Dyn 238:1627-37. 2009
  4. pmc Drosophila TRAP230/240 are essential coactivators for Atonal in retinal neurogenesis
    Janghoo Lim
    Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
    Dev Biol 308:322-30. 2007
  5. ncbi request reprint Lobe and Serrate are required for cell survival during early eye development in Drosophila
    Amit Singh
    Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
    Development 133:4771-81. 2006
  6. pmc Genetic interaction of Lobe with its modifiers in dorsoventral patterning and growth of the Drosophila eye
    Amit Singh
    Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA
    Genetics 171:169-83. 2005
  7. ncbi request reprint Dorso-ventral asymmetric functions of teashirt in Drosophila eye development depend on spatial cues provided by early DV patterning genes
    Amit Singh
    Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
    Mech Dev 121:365-70. 2004
  8. ncbi request reprint Eyeless collaborates with Hedgehog and Decapentaplegic signaling in Drosophila eye induction
    Madhuri Kango-Singh
    Institute of Molecular Biology, Academia Sinica, Nankang, Taipei 11529, Taiwan, Republic of China
    Dev Biol 256:49-60. 2003
  9. ncbi request reprint Eye suppression, a novel function of teashirt, requires Wingless signaling
    Amit Singh
    Institute of Molecular Biology, Academia Sinica, Nankang, Taipei, 11529 Taiwan, Republic of China
    Development 129:4271-80. 2002
  10. ncbi request reprint The wings of Bombyx mori develop from larval discs exhibiting an early differentiated state: a preliminary report
    M Kango-Singh
    Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560 012, India
    J Biosci 26:167-77. 2001

Collaborators

  • Kwang Wook Choi
  • P Sinha
  • Madhuri Kango-Singh
  • Sarah M Oros
  • Janghoo Lim
  • M Kango-Singh
  • Meghana Tare
  • Ok kyung Lee
  • Ya Chieh Hsu
  • Y Henry Sun
  • K P Gopinathan

Detail Information

Publications13

  1. ncbi request reprint An improved method for chemical devitellinization of X-gal stained Drosophila embryos
    A Singh
    Drosophila Stock Center, School of Life Science, Indore, India
    Indian J Exp Biol 33:150-2. 1995
    ..This results in the flaky appearance of the blue stain. We present here an improved chemical devitellinization technique which gives a high yield of devitellinized embryos and a better resolution of the X-gal staining pattern...
  2. pmc Dorsal eye selector pannier (pnr) suppresses the eye fate to define dorsal margin of the Drosophila eye
    Sarah M Oros
    University of Dayton, Dayton, OH 45469, USA
    Dev Biol 346:258-71. 2010
    ..These studies will help in understanding the developmental regulation of boundary formation of the eye field on the dorsal eye margin...
  3. doi request reprint Regulation of organ size: insights from the Drosophila Hippo signaling pathway
    Madhuri Kango-Singh
    Division of Basic Sciences, Mercer University School of Medicine, Macon, Georgia 31207, USA
    Dev Dyn 238:1627-37. 2009
    ..Finally, we will discuss the mammalian Hippo pathway, and its implications in regulation of growth/proliferation during development and disease...
  4. pmc Drosophila TRAP230/240 are essential coactivators for Atonal in retinal neurogenesis
    Janghoo Lim
    Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
    Dev Biol 308:322-30. 2007
    ..We also show that Skd forms a protein complex with Ato in vivo. These data suggest that Kto/Skd act as essential coactivators for Ato expression during early retinal neurogenesis...
  5. ncbi request reprint Lobe and Serrate are required for cell survival during early eye development in Drosophila
    Amit Singh
    Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
    Development 133:4771-81. 2006
    ..5-fold higher frequency. This suggests that L or Ser loss-of-function triggers both caspase-dependent and -independent cell death. Our studies thus identify a mechanism responsible for cell survival in the early eye...
  6. pmc Genetic interaction of Lobe with its modifiers in dorsoventral patterning and growth of the Drosophila eye
    Amit Singh
    Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA
    Genetics 171:169-83. 2005
    ..Our results suggest that L function is regulated by multiple signaling pathways and that the mutual antagonism between L and dorsal genes is crucial for balanced eye growth...
  7. ncbi request reprint Dorso-ventral asymmetric functions of teashirt in Drosophila eye development depend on spatial cues provided by early DV patterning genes
    Amit Singh
    Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
    Mech Dev 121:365-70. 2004
    ..We propose that DV asymmetric function of tsh represents a novel tier of DV pattern regulation, which takes place after the spatial expression patterns of early DV patterning genes are established in the eye...
  8. ncbi request reprint Eyeless collaborates with Hedgehog and Decapentaplegic signaling in Drosophila eye induction
    Madhuri Kango-Singh
    Institute of Molecular Biology, Academia Sinica, Nankang, Taipei 11529, Taiwan, Republic of China
    Dev Biol 256:49-60. 2003
    ..Coexpression experiments show that EY needs to collaborate with high level of HH and DPP to induce ectopic eye formation. Ectopic eye formation also requires the activation of an eye-specific enhancer of the endogenous hh gene...
  9. ncbi request reprint Eye suppression, a novel function of teashirt, requires Wingless signaling
    Amit Singh
    Institute of Molecular Biology, Academia Sinica, Nankang, Taipei, 11529 Taiwan, Republic of China
    Development 129:4271-80. 2002
    ..It affects both growth of eye disc and retinal cell differentiation...
  10. ncbi request reprint The wings of Bombyx mori develop from larval discs exhibiting an early differentiated state: a preliminary report
    M Kango-Singh
    Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560 012, India
    J Biosci 26:167-77. 2001
    ..mori. The timings of morphogenetic events are different and the wing discs behave like presumptive wing buds opening out as wing blades in B. mori unlike evagination of only the pouch region as wing blades seen in Drosophila...
  11. pmc Opposing interactions between homothorax and Lobe define the ventral eye margin of Drosophila eye
    Amit Singh
    Department of Biology, University of Dayton, OH 45469, USA
    Dev Biol 359:199-208. 2011
    ..Further, Exd is not a critical rate-limiting factor for the Hth function. Thus, optimum levels of L and Hth are required to define the boundary between the developing eye and head cuticle on the ventral margin...
  12. doi request reprint A glimpse into dorso-ventral patterning of the Drosophila eye
    Amit Singh
    Department of Biology, University of Dayton, Dayton, Ohio 45469, USA
    Dev Dyn 241:69-84. 2012
    ....